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Animal Models and Cell Lines

>Double Humanized Immune-Checkpoint Mice

B-hPD-1/hLAG3 mice


Basic characteristics

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Targeting strategy

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Protein expression analysis 

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Fig 1. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. Mouse LAG3+ T cells were detectable in both WT C57BL/6 and the homozygous B-hPD-1/hLAG3 mice, while human LAG3+ T cells were detectable in the homozygous B-hPD-1/hLAG3 mice. This might result from the cross-recognition of hLAG3 by anti-mLAG3 antibodies.


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Fig 2. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. Mouse PD-1+ T cells were detectable in the WT C57BL/6 mice, while human PD-1+ T cells were detectable in the homozygous B-hPD-1/hLAG3 mice.



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Fig 3.  Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. Mouse PD-1+/LAG3+ T cells were detectable in the WT C57BL/6 mice, while mouse LAG3+ T cells were detectable in the homozygous B-hPD-1/hLAG3 mice, which might result from the cross-recognition of hLAG3 by anti-mLAG3 antibodies.

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Fig 4. Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hPD-1/hLAG3 mice were analyzed by flow cytometry. Human PD-1+/LAG3+ T cells were detectable in homozygous B-hPD-1/hLAG3 mice.


Combination therapy of PD-1(Keytruda) Ab and LAG3 Ab


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Fig 5. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hLAG3 mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). Anti-hLAG3 antibody shows no inhibitory effects, while the anti-hPD-1 antibody Keytruda shows modest tumor growth inhibition. On the other hand, combination of anti-hLAG3 antibody and the anti-hPD-1 antibody Keytruda shows more significant inhibition when compared to single Ab treatment. B-hPD-1 /hLAG3 mouse model is a powerful tool for in vivo efficacy evaluation of hPD-1 and hLAG3 antibody combination therapy. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.



 

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